Tremor in Parkinson's disease is a common and highly burdensome symptom. Recent evidence shows that areas in the brain that are underlying Parkinson's tremor overlap with those that respond to somatosensory stimulation. Applying such stimulation to the tremulous limb might therefore influence tremor-related brain activity and thereby potentially reduce tremor. In this study, the investigators explore this possibility and investigate whether tremor specific vibrotactile stimulation at the wrist of the most affected arm influences tremor severity.
Parkinson's disease (PD) is the second most common neurodegenerative disease, of which tremor is a common and highly burdensome symptom. The pathophysiology of tremor involves a cerebral network that consists of basal ganglia and a cerebello-thalamo-cortical motor circuit. Emerging evidence suggests that somatosensory input from the tremulous limb to the brain may influence this network. Specifically, tremor-related activity was observed in primary and secondary somatosensory cortex, and thalamic cells involved in tremor appear to be responsive to somatosensory stimulation as well. Somatosensory afferents may thus play a role in tremor pathophysiology and could therefore be used as treatment target. Here, the investigators will test this hypothesis by investigating the effect of modulating somatosensory input (with vibrotactile stimulation) on tremor severity. The primary objectives are 1) to test whether rhythmic somatosensory input (vibrotactile stimulation) at tremor frequency reduces tremor power of Parkinson's tremor as compared to vibrotactile stimulation at 1.5 times tremor frequency and 2) whether continuous 80Hz vibrotactile stimulation reduces tremor power as compared to sham stimulation. As secondary objectives, the investigators will test whether the effect of vibrotactile stimulation on tremor power depends on the context in which tremor occurs (rest, cognitive coactivation, posture), whether stimulation at tremor frequency reduces tremor power as compared to sham stimulation, and whether vibrotactile stimulation has an effect on two other common PD symptoms: impaired gait and bradykinesia. The investigators will include 27 patients with Parkinson's disease and rest as well as postural tremor. The intervention involves subtle mechanical vibrations on the wrist or ankles. This is a non-invasive and painless way to provide somatosensory stimuli, in a continuous (80Hz) or rhythmic fashion (brief bursts of 80 Hz at tremor or step frequency). The investigators expect that this study will provide mechanistic insights into if and how somatosensory (vibro-tactile) afferents influence the cerebral tremor circuit in Parkinson's disease, and may provide a solid basis for designing further clinical treatment studies.
Mechanical vibrations are applied at brief bursts of 80Hz that occur at the individual tremor frequency. Vibrations are delivered via a small device, which is worn on the wrist of the most-affected arm.
Mechanical vibrations are applied at 80Hz bursts at individual tremor frequency\*1.5. Vibrations are delivered via a small device, which is worn on the wrist of the most-affected arm.
Continuous 80Hz stimulation is applied via a small device worn on the wrist of the most-affected arm.
Donders Centre for Cognitive Neuroimaging
Nijmegen, Gelderland, Netherlands
The effect of vibrotactile stimulation at tremor frequency on tremor severity with active control
The investigators will investigate the effect of frequency specific stimulation compared to an active control condition, averaged across three different contexts (rest/posture/cognitive coactivation). Specifically, we will test the change in log transformed tremor power from baseline to stimulation, as a function of stimulation setting (bursts at tremor frequency vs. bursts at 1.5 times tremor frequency).
Time frame: 25 minutes
The effect of continuous vibrotactile stimulation on tremor severity
The investigators will investigate the effect of continuous stimulation compared to sham stimulation, averaged across three different contexts (rest/posture/cognitive coactivation). Specifically, we will test the change in log transformed tremor power from baseline to stimulation, as a function of stimulation setting (continuous 80Hz stimulation vs. sham). For the two primary outcomes measures, Bonferroni correction will be applied to correct for multiple comparisons.
Time frame: 25 minutes
The effect of vibrotactile stimulation at tremor frequency on tremor severity with passive control
The investigators will explore the change in log transformed tremor power from baseline to stimulation, as a function of stimulation setting (bursts at tremor frequency vs. sham).
Time frame: 25 minutes
The effect of continuous vibrotactile stimulation on bradykinesia
The average button presses per second in the keyboard finger tapping test during continuous 80Hz stimulation versus sham will be investigated.
Time frame: 10 minutes
The effect of vibrotactile stimulation on gait
Time to complete the timed up and go task will be investigated, comparing stimulation 10% above step frequency/10% below step frequency/sham
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Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
34
This intervention is applied during assessment of gait. Two devices are worn on both ankles which allows alternating stimulation of both ankles with brief bursts of 80 HZ at the individual step frequency plus or minus 10%.
Time frame: 10 minutes
The effect of vibrotactile stimulation on freezing
Number of freezing episodes during the timed up and go task will be investigated, comparing stimulation 10% above step frequency/10% below step frequency/sham
Time frame: 10 minutes
Investigating the effect of vibrotactile stimulation at tremor frequency on tremor severity in 3 different contexts
The investigators will explore the change in log transformed tremor power from baseline to stimulation as a function of stimulation setting (bursts at tremor frequency/bursts at 1.5 times tremor frequency) and context (rest/posture/cognitive coactivation).
Time frame: 25 minutes
Investigating the effect of continuous stimulation on tremor severity in 3 different contexts
The investigators will explore the change in log transformed tremor power from baseline to stimulation, as a function of stimulation setting (continuous 80Hz stimulation vs. sham) and context (rest/posture/cognitive coactivation).
Time frame: 25 minutes